Modulation of the immune response to tumor cells and to conventional antigens by non-specific factors will be examined in the experimental program proposed. Major emphasis will be placed on defining and understanding the cellular basis for the immunostimulatory properties of a methanol extraction residue (MER) of BCG, a material which induces resistance to syngeneic tumors and elevates antibody formation and cellular immunity. The effects of MER on different T cell (thymus-derived lymphocyte)activities and on subpopulations of T cells will be examined, and the optimal conditions for achieving such effects determined. Optimal conditions for increasing the activity of lymphoid cells which recognize and are cytotoxic for tumor specific transplantation antigens will be determined. Another line of work will compare the triggering of B cells by T cell dependent and T cell independent signals. Since BCG has been used extensively in a clinical setting, it is essential that similar and less toxin materials (such as MER) are examined under laboratory conditions to determine their mode of action for possible clinical applications in the control of neoplastic disease. The proposed program should result in ascertaining the possible usefulness and safety of such preparations.